In recent years, intensive studies have been made on the magnetic particle-containing drugs in the form of a composite material comprising magnetic iron oxide fine particles as a magnetic material and a biocompatible substance such as phospholipids, proteins and water-soluble polymers (Patent Documents 1 to 5, etc.).
In addition, in order to prepare a monodisperse aqueous solution of the magnetic iron oxide fine particles, there are known a method of coating a surface of the respective particles with a surface-treating agent such as surfactants (Patent Document 6); a method of coating a surface of the respective particles with an inorganic material such as Al and Si (Patent Document 7); a method of coating a surface of the respective particles with an organic metal polymer (Patent Document 4); a method of preparing the monodisperse aqueous solution without using any dispersant (Patent Document 8), etc.; or the like.
Further, it has been reported that in order to facilitate bonding between the magnetic iron oxide particles and vital molecules, the surface of the respective magnetic iron oxide particles is coated with a surface-modifying molecule having a functional group such as an amino group, a carboxyl group and a sulfone group (Patent Documents 9 to 11).
In any of these conventional arts, after once preparing an aqueous sol of iron oxide, the aqueous sol is mixed with respective polymers or polysaccharides. For this reason, the resulting magnetic particles have a large particle diameter owing to aggregation thereof, or these magnetic particles are merely weakly bonded to the surface-modifying molecule so that they tend to be readily dissociated from each other in blood and deteriorated in stability upon heat sterilization and stability with time.
In particular, the fine magnetic iron oxide particles may hardly be uniformly dispersed in the biocompatible substance and supported thereon owing to occurrence of excessive magnetic aggregation between the iron oxide particles. For this reason, the conventional magnetic iron oxide particles used for this purpose inevitably have a large particle diameter.
Also, there is a high possibility that the magnetic iron oxide particles having a large particle diameter remain in vivo after therapies. In addition, the magnetic iron oxide particles remaining in vivo may cause side reactions such as allergy reaction. Thus, the conventional magnetic iron oxide particles have failed to ensure a sufficient safety upon use thereof.
In consequence, there is an increasing demand for development of a raw drug for magnetic particle-containing drugs which is capable of producing the magnetic particle-containing drugs for diagnosis and therapies which can exhibit excellent stability and retentivity in blood and further can form a peculiar compatible bond to specific target molecules in view of tumor deposition, with a good reproducibility.